SummaryTwo strains of mice were used in this project. Female C3H and CBA mice were exposed to a total body dose of radiation of 3 Gy with or without Tempol supplementation in the animal's food. Immediately following the radiation exposure, animals were be placed on either control or TP-containing food. The groups include: a) no radiation, control food, b) 3 Gy, control food, c) no radiation, TP food, and d) 3 Gy, TP food. Animals (&gt;1200 mice) were monitored for their entire lifespan and upon development of a tumor or when a humane endpoint was reached mice were euthanized, necropsied, and evaluated pathologically for the presence of tumor and cause of death. Chronic supplementation of TP in the diet of mice reduced body weight without toxicity, decreased cancer, and extended survival when administered after non-lethal total body radiation (TBI). Notably, delaying administration of the Tempol diet 1 month after TBI could also enhance survival. Tempol reduced the incidence of hematopoietic neoplasms (lymphomas) in both mouse strains; whereas, both the onset and incidence of non-hematopoietic neoplasms were reduced in CBA mice. Interestingly it was shown that the lifespan of unirradiated mice on control versus Tempol-containing food was the same, suggesting that reduced weights over a lifespan does not enhance the lifespan. These results encourage further study of Tempol as a chemopreventive, to reduce the incidence of radiation-induced second malignancies after a course of definitive radiation therapy. Tempol may also find applications to reduce the risk of cancers in populations exposed to non-lethal radiation due to nuclear accidents or terrorist attacks.Data are currently being analyzed from a study testing the hypothesis that mice protected from lethal total body irradiation by administration of a radioprotector immediately before radiation exposure will experience an elevated risk of cancer induction. Mice were exposed to a total body radiation dose of 10.8 Gy, a radiation dose that results in 100% lethality. Ten minutes prior to the 10.8 Gy exposure the animals will be injected with a radioprotector. The control for this group, another set of animals was exposed to 5.4 Gy total body irradiation. This radiation dose was derived from the radiation dose modification factor (2) when the radioprotector is administered 10 min before total body irradiation. These animals were followed for their entire lifespan for tumor induction as outlined above. The median survival for mice receiving 0, 5.4 or 10.8 Gy was 706, 460, and 491 days, respectively. There was no difference between the 5.4 and 10.8 Gy groups (p = 0.42); however, the median survival of both irradiated groups was significantly shorter compared to unirradiated mice (p &lt; 0.0001). Cancer incidence (hematopoietic plus solid tumors) was similar between the 5.4 and 10.8 Gy groups and was significantly greater than for unirradiated controls. These data suggest that mice protected from lethal whole body radiation have a shortened lifespan, due in large part, to cancer induction post-radiation compared to unirradiated controls.Lastly, studies are on-going to determine if metabolites in the urine of mice receiving whole body radiation can predict for radiation-induced cancer induction prior to the observation of tumor mass.